INTRODUCTION TO NORMAL PHYSIOLOGY CELL PHYSIOLOGY Lecture 1

INTRODUCTION TO NORMAL PHYSIOLOGY. CELL PHYSIOLOGY Lecture 1 2014 Irina Vasilyevna Mukhina Professor Ph. D DSci Head of Normal Physiology Department of Nizhny Novgorod Medical State Academy

Physiology is ¤the study of the function of all plants and animals in their normal state. ¤an integrative science Figure 1 -1: Levels of organization and the related fields of study

Animal physiology Vertebrates Mammalian physiology Human (Normal) physiology Invertebrates

The Human Physiology • Normal (human) physiology is the study of normal body function (in a healthy state).

Review Levels of Organization Homo sapiens

Why is the study of human physiology so important? • Human physiology is the major scientific foundation of medicine and other health applications. • We must understand how a cell, tissue, organ, or system normally functions (its normal physiology) before we can understand how the physiological processes become altered in disease or injury, which is a related science known as pathophysiology.

Distinguish between Process & Function How do we breathe? Why do we breathe? How does blood flow? Why does blood flow? How do RBCs transport O 2? Why do RBC transport O 2? Integrate both for complete picture!

General physiology of excitable tissues

• The irritability is ability of the biosystems to answer the stimulation or action of external and internal environment by means of change in cell metabolism. • Excitability is ability of the nervous, muscle and secretory tissues to answer the stimulation by means of rapid membrane depolarization or action potential generation. • Excitation is process of action potential generation. • Reciprocal response can be: • neuron - a nervous impulse, • muscle cell - contract, • secretory cell - synthesis and excretory an active matter.

“animal electricity” History • A. Galvani (1737 -1798)

А. Volta (1745 -1827) “metal electricity”

General Physiologic Processes. CELL STRUCTURE AND FUNCTION

Plasma Membrane The plasma membrane defines the perimeter of the cell. Its special composition allows: 1. Export/import functions of substances that were synthesized or are to be metabolized within the cell; 2. Control of intracellular composition; 3. Recognition of other cells, and 4. Interaction with neighboring cells.

Membrane Structure The two major components are lipids and proteins in proportions that vary among different tissues. • The lipids can both rotate and move laterally within their membrane leaf. • The proteins are relatively fixed in position because of cytoskeletal anchoring.

The fluid-mosaic model of the plasma membrane

Components of the Plasma Membrane

Membrane Function. Membrane transport mechanisms The plasma membrane separates the cytosole from extracellular space and maintains the highly unequal ion concentrations of the two spaces. This is accomplished by four membrane transport strategies: 1. Diffusion; 2. Osmos; 3. Active transport; 4. Vesicular transport.

1. Diffusion Gases and lipid-soluble molecules cross the membrane by simple diffusion through the lipid phase and are driven down their concentration gradients; Water-soluble molecules cross the membrane by diffusion through the channels (simple diffusion) and through the carrier (facilitated diffusion).

• Carriers that transfer a single solute across the membrane are called uniports • There also carriers that transport two or more solute species such that the transfer of one depends on the coupled transfer of the others, either in the same direction (symport) or in the opposite direction (antiport).

Passive membrane transport mechanisms

Simple diffusion Ion channels Gated control Voltage-gated Ligand-gated Schema of a typical ion channel Without Gated control Mechanical -gated

2. Osmos

3. Active membrane transport mechanisms

3 a. Primary active transport

3 b. Secondary active transport

4. Vesicular transport • Macromolecules, such as proteins, are transported in carrier vesicles either out of the cell (exocytosis) or into the cell (endocytosis).

Resting membrane potential

• The current arises between the damaged (injured) and intact site of a membrane is called resting current. • The current arises between the exited and not exited site of a membrane is called current of action.

Origin of (resting) membrane potential • The potential difference across the cell membrane (transmembrane) is resting membrane potential. Various theories have been put forward to The membrane-ion theory by Hodgkin and Huxley (1949 -52) is explained the nature of resting potential.

PATCH-CLAMP E. Neher B. Sakmann Nobel Price -1991

Resting membrane potential (RMP or MP) is predetermined by : 1. Electrochemical gradient. It is determined by both electrical and concentration forces. According to the laws of an electrostatics unlikes (positive and negative charges) attract and likes are repelled. Unequal concentration of potassium, sodium and chlorine ions within the cell and outside its. Ions pass on a concentration gradient. 2. Variable permeability of the surface of the membrane to ions. 3. Sodium-potassium pump or Na+ - K+ ATPase

1. Electrochemical gradient. • Equilibrium potential is calculated with the Nernst’s equation which is determined by both electrical and concentration forces. Eion = 61. 5 log Cout/Cin • EK = -90 m. V ENa = +60 m. V ECl = -70 m. V The resting membrane potential EM = -70 m. V (Goldman-Hodgkin-Katz)

2. The variable permeability of the membrane to ions depends on the structure and function of protein channels. The selectivity of channels is caused by: 1. Geometry of channels (size and selectivity of the filter, negative charge on a internal surface of the channel). 2. Gated mechanism of the channel. 3. Electrical charge of environmental structures or receptors, or stretching. K+ - Na+ - Cl 1 : 0, 04 : 0, 45

Schematic of a typical ion channel

Ion channels Gated Electrical (Voltage-gated channels) Ungated Chemical (Ligand-gated channels) Mechanical (Stretch -gated channels)

3. Sodium-potassium pump

CHECK POINT 1. The membrane potential will depolarize by the greatest amount if the membrane permeability increases for which of the following? a. K+ b. Na+ and K+ c. Cld. Na+ 2. A fireman suffers extensive burns, resulting in a fluid and electrolyte imbalance. Which of the following conditions will produce a decrease in the magnitude of a nerve membrane action potential? • a. Hyperkalemia b. Hypokalemia • c. Hypernatremia d. Hyponatremia

Thank you!